Integrative Approaches Identify Genetic Determinants of Levodopa Induced Dyskinesia
文献类型：期刊论文
| 作者 | Wan, Ying15; Rong, Lu15; Li, Qingyuan12,13,14; Liu, Suzhi11; Li, Wentao10; Ye, Min9; Luo, Weifeng6,7,8; Xie, Anmu5; Shao, Jingsong4; Guo, Dengjun3 |
| 刊名 | MOLECULAR NEUROBIOLOGY
 |
| 出版日期 | 2025-04-29 |
| 页码 | 9 |
| 关键词 | Parkinson's disease Levodopa induced dyskinesia Genetic determinants Integrative analysis Interventional targets |
| ISSN号 | 0893-7648 |
| DOI | 10.1007/s12035-025-04930-5 |
| 通讯作者 | Liu, Zhenguo(liuzhenguo@xinhuamed.com.cn) |
| 英文摘要 | Levodopa induced dyskinesia (LID) is a serious side effect of levodopa treatment in Parkinson's disease (PD), with limited interventions. Understanding the genetic impact on LID would help inform future intervention studies. We performed integrative genomic analysis approaches to identify the genetic determinants of LID in a Chinese multi-center prospective, observational PD cohort. In this cohort, 46 of 315 PD patients developed LID during 2.5 years of follow-up. First, we performed a genome-wide association study (GWAS) in this cohort, followed by a meta-analysis integrating our GWAS summary data with additional data of European ancestry. Both GWAS analyses identified the Bromodomain Containing 3 (BRD3) as a LID susceptibility gene (P < 5 x 10(-8)); however, the genetic variants within the BRD3 gene differed between the analyses. Then, we conducted a multi-tissue transcriptome-wide association study (TWAS) through integrating our GWAS summary data with six gene expression quantitative trait loci (eQTLs) datasets from tissues involved in the levodopa transport-to-function pathway, including stomach, blood, caudate, putamen, nucleus accumbens, and frontal cortex. We found that the expression levels of the TRAPPC12 Antisense RNA 1 (TRAPPC12-AS1) and Williams Beuren Syndrome Chromosome Region 27 (WBSCR27) in all tissues were associated with LID occurrence. Finally, we executed the summary data-based mendelian randomization (SMR) and identified that LID was causally associated with the two genes' expression in all tissues. In conclusion, our findings support new candidate genes for LID susceptibility, providing novel potential targets for future intervention studies. |
| WOS关键词 | ASSOCIATION ; GWAS ; EQTL |
| 资助项目 | National Key Research and Development Program of China |
| WOS研究方向 | Neurosciences & Neurology |
| 语种 | 英语 |
| WOS记录号 | WOS:001478889900001 |
| 出版者 | SPRINGER |
| 源URL | [http://ir.qdio.ac.cn/handle/337002/201751]  |
| 专题 | 海洋研究所_实验海洋生物学重点实验室 |
| 通讯作者 | Liu, Zhenguo |
| 作者单位 | 1.Nanjing Med Univ, Affiliated Hosp 1, Dept Neurol, Nanjing, Jiangsu, Peoples R China 2.First Peoples Hosp Linan Dist, Dept Neurol, Hangzhou, Zhejiang, Peoples R China 3.Tongde Hosp Zhejiang Prov, Dept Neurol, Hangzhou, Zhejiang, Peoples R China 4.Shaoxing Hosp Tradit Chinese Med, Dept Neurol, Shaoxing, Zhejiang, Peoples R China 5.Qingdao Univ, Dept Neurol, Affiliated Hosp, Qingdao, Shandong, Peoples R China 6.Soochow Univ, Jiangsu Key Lab Translat Res & Therapy Neuropsychi, Suzhou, Jiangsu, Peoples R China 7.Soochow Univ, Affiliated Hosp 2, Suzhou Clin Res Ctr Neurol Dis, Suzhou, Jiangsu, Peoples R China 8.Soochow Univ, Affiliated Hosp 2, Dept Neurol, Suzhou, Jiangsu, Peoples R China 9.Nanjing Med Univ, Affiliated BenQ Hosp, BenQ Med Ctr, Dept Neurol, Nanjing, Jiangsu, Peoples R China 10.Shanghai Univ Tradit Chinese Med, Dept Neurol, Shanghai Municipal Hosp Tradit Chinese Med, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wan, Ying,Rong, Lu,Li, Qingyuan,et al. Integrative Approaches Identify Genetic Determinants of Levodopa Induced Dyskinesia[J]. MOLECULAR NEUROBIOLOGY,2025:9. |
| APA | Wan, Ying.,Rong, Lu.,Li, Qingyuan.,Liu, Suzhi.,Li, Wentao.,...&Liu, Zhenguo.(2025).Integrative Approaches Identify Genetic Determinants of Levodopa Induced Dyskinesia.MOLECULAR NEUROBIOLOGY,9. |
| MLA | Wan, Ying,et al."Integrative Approaches Identify Genetic Determinants of Levodopa Induced Dyskinesia".MOLECULAR NEUROBIOLOGY (2025):9. |
入库方式： OAI收割
来源：海洋研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。